Bone is a randomized, complex porous network which researchers have tried to mimic within bone tissue engineering scaffolds. The objective of this study was to understand the effects of random and controlled scaffold porosity on the release kinetics of vitamin D3 to determine if a designed porous structure was comparable in effectiveness on osteoblast proliferation to the randomized essence of natural bone. In this study, porous tricalcium phosphate (TCP) scaffolds were prepared by fugitive material removal method using naphthalene and 3D printing to model random and controlled porosity, respectively. Scaffold comparison was made based on open pore volume percentage of which naphthalene scaffolds had 45.8 ± 1.5% and 3D printed scaffolds had 48.9 ± 2.5%, Comparative analysis of traditional bioceramic processing to additive manufacturing is limited especially regarding drug release kinetics. Results showed the naphthalene scaffold surface area was only 0.3% that of 3D printed scaffolds due to the lower open pore interconnectivity. This increase in surface area produced higher release of drug and osteoblast proliferation in 3D printed scaffolds comparatively. By 11 days, osteoblast proliferation was enhanced by 64% from scaffolds manufactured using 3D printing compared to traditional processing. Understanding the effects of processing methods of TCP scaffolds on the release kinetics of vitamin D3 and the system effects on cells can aid in low load bearing applications for bone tissue engineering.
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Human fetal osteoblast
Attenuated Total Reflection-Fourier Transform Infrared
Field Emission Scanning Electron Microscopy
Phosphate buffer solution
Acetate buffer solution
Dulbecco’s Modified Eagle’s Medium
Fetal bovine serum
- MTT assay:
30 wt% naphthalene in TCP scaffolds
350 μm designed pore size 3DP TCP scaffolds
Bose, S., D. Banerjee, S. Robertson, and S. Vahabzadeh. Enhanced in vivo bone and blood vessel formation by iron oxide and silica doped 3D printed tricalcium phosphate scaffolds. Ann. Biomed. Eng. 46(9):1241–1253, 2018.
Bose, S., N. Sarkar, and D. Banerjee. Effects of PCL, PEG and PLGA polymers on curcumin release from calcium phosphate matrix for in vitro and in vivo bone regeneration. Mater. Today Chem. 8:110–120, 2018.
Bose, S., S. Vahabzadeh, and A. Bandyopadhyay. Bone tissue engineering using 3D printing. Mater. Today 16:496–504, 2013.
Daculsi, G., and N. Passuti. Effect of the macroporosity for osseous substitution of calcium phosphate ceramics. Biomaterials 11:86–87, 1990.
Daculsi, G., N. Passuti, S. Martin, C. Deudon, R. Z. Legeros, and S. Raher. Macroporous calcium phosphate ceramic for long bone surgery in humans and dogs. Clinical and histological study. J. Biomed. Mater. Res. 24:379–396, 1990.
Gbureck, U., O. Grolms, J. E. Barralet, L. M. Grover, and R. Thull. Mechanical activation and cement formation of β-tricalcium phosphate. Biomaterials 24:4123–4131, 2003.
Hoch, A. I., R. Duhr, N. Di Maggio, A. Mehrkens, M. Jakob, and D. Wendt. Expansion of bone marrow mesenchymal stromal cells in perfused 3D ceramic scaffolds enhances in vivo bone formation. Biotechnol. J. 12:1700071, 2017.
Ke, D., W. Dernell, A. Bandyopadhyay, and S. Bose. Doped tricalcium phosphate scaffolds by thermal decomposition of naphthalene: mechanical properties and in vivo osteogenesis in a rabbit femur model. J. Biomed. Mater. Res. B. Appl. Biomater. 103:1549–1559, 2015.
Ke, D., S. Tarafder, S. Vahabzadeh, and S. Bose. Effects of MgO, ZnO, SrO, and SiO2 in tricalcium phosphate scaffolds on in vitro gene expression and in vivo osteogenesis. Mater. Sci. Eng. C. 96:10–19, 2019.
Laurencin, C., Y. Khan, and S. F. El-Amin. Bone graft substitutes. Exp. Rev. Med. Dev. 3:49–57, 2006.
Liu, D. M. Fabrication of hydroxyapatite ceramic with controlled porosity. J. Mater. Sci. Mater. Med. 8:227–232, 1997.
Mastrogiacomo, M., A. Papadimitropoulos, A. Cedola, F. Peyrin, P. Giannoni, S. G. Pearce, M. Alini, C. Giannini, A. Guagliardi, and R. Cancedda. Engineering of bone using bone marrow stromal cells and a silicon-stabilized tricalcium phosphate bioceramic: evidence for a coupling between bone formation and scaffold resorption. Biomaterials 28:1376–1384, 2007.
Miao, X., D. M. Tan, J. Li, Y. Xiao, and R. Crawford. Mechanical and biological properties of hydroxyapatite/tricalcium phosphate scaffolds coated with poly (lactic-co-glycolic acid). Acta Biomater. 4:638–645, 2008.
Miranda, P., E. Saiz, K. Gryn, and A. P. Tomsia. Sintering and robocasting of β-tricalcium phosphate scaffolds for orthopaedic applications. Acta Biomater. 2:457–466, 2006.
Mumford, J. E., and A. H. R. W. Simpson. Management of bone defects: a review of available techniques. Iowa Orthop. J. 12:42, 1992.
Murphy, C. M., M. G. Haugh, and F. J. O’Brien. The effect of mean pore size on cell attachment, proliferation and migration in collagen-glycosaminoglycan scaffolds for bone tissue engineering. Biomaterials 31:461–466, 2010.
Phipps, M. C., W. C. Clem, J. M. Grunda, G. A. Clines, and S. L. Bellis. Increasing the pore sizes of bone-mimetic electrospun scaffolds comprised of polycaprolactone, collagen I and hydroxyapatite to enhance cell infiltration. Biomaterials 33:524–534, 2012.
Pneumaticos, S. G., G. K. Triantafyllopoulos, E. K. Basdra, and A. G. Papavassiliou. Segmental bone defects: from cellular and molecular pathways to the development of novel biological treatments. J. Cell. Mol. Med. 14:2561–2569, 2010.
Rai, B., M. E. Oest, K. M. Dupont, K. H. Ho, S. H. Teoh, and R. E. Guldberg. Combination of platelet-rich plasma with polycaprolactone-tricalcium phosphate scaffolds for segmental bone defect repair. J. Biomed. Mater. Res. A. 81:888–899, 2007.
Sabree, I., J. E. Gough, and B. Derby. Mechanical properties of porous ceramic scaffolds: influence of internal dimensions. Ceram. Int. 41:8425–8432, 2015.
Sohier, J., G. Daculsi, S. Sourice, K. De Groot, and P. Layrolle. Porous beta tricalcium phosphate scaffolds used as a BMP-2 delivery system for bone tissue engineering. J. Biomed. Mater Res. A 92:1105–1114, 2010.
Suda, T., F. Takahashi, and N. Takahashi. Bone effects of vitamin D—discrepancies between in vivo and in vitro studies. Arch. Biochem. Biophys. 523:22–29, 2012.
Tarafder, S., V. K. Balla, N. M. Davies, A. Bandyopadhyay, and S. Bose. Microwave-sintered 3D printed tricalcium phosphate scaffolds for bone tissue engineering. J. Tissue Eng. Regen. Med. 7:631–641, 2013.
Van der Stok, J., E. M. Van Lieshout, Y. El-Massoudi, G. H. Van Kralingen, and P. Patka. Bone substitutes in the Netherlands—a systematic literature review. Acta Biomater. 7:739–750, 2011.
Wen, H., Y. Liu, J. Li, D. Wei, D. Liu, and F. Zhao. Inhibitory effect and mechanism of 1,25-dihydroxy vitamin D3 on RANKL expression in fibroblast-like synoviocytes and osteoclast-like cell formation induced by IL-22 in rheumatoid arthritis. Clin. Exp. Rheum. 36:798–805, 2018.
Xue, W., A. Bandyopadhyay, and S. Bose. Polycaprolactone coated porous tricalcium phosphate scaffolds for controlled release of protein for tissue engineering. J. Biomed. Mater. Res. B. Appl. Biomater. 91:831–838, 2009.
Zhang, X. Y., G. Fang, and J. Zhou. Additively manufactured scaffolds for bone tissue engineering and the prediction of their mechanical behavior: A review. Materials 10:50, 2017.
Zolnik, B. S., and D. J. Burgess. Effects of acidic pH on PLGA microsphere degradation and release. J. Control Release 122:338–344, 2007.
Authors would like to acknowledge financial support from the National Institutes of Health under the Grant Number R01 AR066361. The authors would also like to thank Samuel Robertson for his experimental help with this work. Additionally, thank you to the Franceschi Microscopy & Imaging Center at Washington State University. This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Vu, A.A., Bose, S. Vitamin D3 Release from Traditionally and Additively Manufactured Tricalcium Phosphate Bone Tissue Engineering Scaffolds. Ann Biomed Eng 48, 1025–1033 (2020). https://doi.org/10.1007/s10439-019-02292-3
- Bone tissue engineering
- Fugitive material removal
- 3D printing
- Drug delivery